Significance Lung cancer is the leading cause of cancer mortality with a 5-year survival rate of 16% following surgery and intravenous chemotherapy. Problem Despite the use of aggressive surgery and combination chemotherapy, a major limitation in the control of primary and metastatic non-small cell pulmonary tumors with the use of the systemic administration of chemotherapy drugs is the low drug concentration in the lungs due to blood volume dilution and metabolism. There is a critical unmet medical need to develop new strategies to improve patient treatment outcomes. Innovation In contrast to systemic delivery of chemotherapy, inhalation delivers a chemotherapeutic drug directly to tumor tissues in the lung thereby enhancing its efficacy and safety due to increased local drug concentration in the lung, decreased systemic drug levels in the circulation, and decreased systemic toxicity. Gap Preliminary pre-clinical in-vivo studies using nebulized chemotherapy drugs has demonstrated efficacy and established the feasibility of delivery via aerosol, but nebulization of toxic drugs has major drawbacks. These drawbacks include a lack of efficient peripheral airway penetration, high mouth-throat deposition, contamination of equipment, and collateral aerosol risk to medical staff. Project Objective To address these drawbacks, we are developing a new method of delivering a chemotherapeutic drug via inhalation to reach pulmonary tumors directly in order to maximize the effectiveness and safety of the aerosol treatment with a fraction of the standard dose. We will create a novel dry powder chemotherapeutic formulation containing an FDA approved chemotherapy medication for the treatment of non- small cell lung cancer. Aims Aims of this proposal will evaluate the feasibility of manufacturing the novel formulation and then demonstrating efficacy in an established in-vivo lung cancer model. Commercial Potential Translation of this technology into a clinically beneficial inhalable chemotherapy product has the potential to significantly improve the treatment of pulmonary tumors in lung cancer patients by delivering targeted lower doses of medicine directly to the lung while minimizing systemic toxicity.